Comparison of a transdermal contraceptive patch with a newly sourced adhesive component versus EVRA patch: A double-blind, randomized, bioequivalence and adhesion study in healthy women

Contraception. 2020 Apr;101(4):276-282. doi: 10.1016/j.contraception.2019.12.012. Epub 2020 Jan 11.

Abstract

Objective: To evaluate the bioequivalence of norelgestromin and ethinyl estradiol (NGMN-EE) and adhesion of a transdermal contraceptive patch containing a newly sourced adhesive component (test) compared with the marketed (reference) patch.

Study design: In this randomized, double-blind, 2-way crossover study, healthy women received single 7-day application of both test and reference patches. Treatment phase included two treatment periods of 11 days each separated by a 21-day washout period starting from day of patch removal (day 8) of treatment period 1. Assessments included NGMN and EE pharmacokinetics (PK), adhesion using European Medicines Agency (EMA) 5-point scale, irritation potential and application-site reactions, and safety. Patches were bioequivalent if 90% CIs of ratios of means of test/reference for AUC168h, AUCinf, and Css fell within 80-125%. Patch adhesion was comparable if ratios of mean cumulative adhesion percentage values of test/reference were ≥90.0%.

Results: Seventy women were randomized; 57 completed both treatments with ≥80% adhesion (score 0-1). Bioequivalence of test and reference patches was demonstrated as 90% CI of ratio of geometric means for AUC168h, AUCinf, and Css for NGMN and EE fell within 80-125%. Both patches had similar adhesion properties (geometric mean ratio was 100.3% [90% CI, 93.2-107.9]). Similar rates of mild-to-moderate itching (11% vs 10%) and erythema events (79% vs 74%) were reported for test and reference patches, respectively, on day 8.

Conclusions: The test patch with the newly sourced adhesive component is bioequivalent to the currently marketed NGMN-EE transdermal patch and has similar adhesion and irritation potential.

Implications statement: The norelgestromin and ethinyl estradiol transdermal patch containing a newly sourced adhesive component is bioequivalent to the currently marketed patch for both active moieties. Both patches had similar adhesion, irritation potential, and safety profiles.

Keywords: Ethinyl estradiol; Norelgestromin; Patch adhesion; Pharmacokinetics; Polyisobutylene.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesives / administration & dosage
  • Adhesives / adverse effects*
  • Adult
  • Contraceptive Agents, Hormonal / administration & dosage
  • Contraceptive Agents, Hormonal / adverse effects
  • Contraceptive Agents, Hormonal / pharmacokinetics*
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Combinations
  • Ethinyl Estradiol / administration & dosage
  • Ethinyl Estradiol / adverse effects
  • Ethinyl Estradiol / pharmacokinetics*
  • Female
  • Humans
  • Norgestrel / administration & dosage
  • Norgestrel / adverse effects
  • Norgestrel / analogs & derivatives*
  • Norgestrel / pharmacokinetics
  • Therapeutic Equivalency
  • Transdermal Patch / adverse effects*
  • Transdermal Patch / standards

Substances

  • Adhesives
  • Contraceptive Agents, Hormonal
  • Drug Combinations
  • Ortho Evra
  • Norgestrel
  • Ethinyl Estradiol